Bisnaphthalimidopropyl spermidine induces apoptosis within colon carcinoma cells

Lynda D Ralton, Charles S Bestwick, Lesley Milne, Susan Duthie, Paul Kong Thoo Lin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Bisnaphthalimido compounds bisintercalate to DNA via the major groove and are potentially potent cancer therapeutics. We incorporated natural polyamines as linkers connecting the two-naphthalimido ring moieties to create a series of novel soluble cytotoxic bisnaphthalimidopropyl polyamines (BNIPPs). Here, we determined the cytotoxicity of bisnaphthalimidopropyl spermidine (BNIPSpd) towards Caco-2 and HT-29 colon adenocarcinoma cells revealing an IC50 value of 0.15 and 1.64 mu M after 48 h exposure within Caco-2 and HT-29 cells, respectively. After 4 h. >0.5 mu M BNIPSpd treatment-induced significant DNA damage. After 24 h exposure a concentration-dependent increase in active caspase-3 expression, chromatin condensation and internucleosomal DNA fragmentation identified apoptosis as the principal manifestation for the cytotoxicity within both cell lines. By 24 h exposure, there was also a significant decline in cellular spermine and spermidine levels. It is concluded that bisnaphthalimidopropyl spermidine (BNIPSpd) toxicity primarily results from apoptosis and that BNISpd has potential to be further developed as an anti-tumour agent.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalChemico-Biological Interactions
Volume177
Issue number1
Early online date15 Oct 2008
DOIs
Publication statusPublished - 15 Jan 2009

Keywords

  • DNA damage
  • bisnaphthalimidopropylpolyamines
  • polyamines
  • apoptosis
  • colon cancer
  • improved seperation systems
  • oxidative DNA-damage
  • bis-naphthalimides
  • polyamine depletion
  • liquid-chromatography
  • biological-activities
  • antitumor agents
  • in-vitro
  • derivatives
  • anoikis

Cite this

Bisnaphthalimidopropyl spermidine induces apoptosis within colon carcinoma cells. / Ralton, Lynda D; Bestwick, Charles S; Milne, Lesley; Duthie, Susan; Lin, Paul Kong Thoo.

In: Chemico-Biological Interactions, Vol. 177, No. 1, 15.01.2009, p. 1-6.

Research output: Contribution to journalArticle

Ralton, Lynda D ; Bestwick, Charles S ; Milne, Lesley ; Duthie, Susan ; Lin, Paul Kong Thoo. / Bisnaphthalimidopropyl spermidine induces apoptosis within colon carcinoma cells. In: Chemico-Biological Interactions. 2009 ; Vol. 177, No. 1. pp. 1-6.
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